The goals of the project are to are to use resonance Raman spectroscopy (RRS) and heavy water labeling as a metabolic fingerprinting tool to distinguish different subtypes of breast cancer, and to use multiphoton fluorescence microscopy to detect native fluorescence signals from critical metabolic molecules (collagen, tryptophan, NADH, flavin, etc.) in aggressive and less aggressive tumors. We will further explore the mechanism for the differences in metabolism by studying tumor metabolism by in vivo measurements of glycolytic changes, a critical metabolic pathway in tumors, and tumor perfusion. The latter is critical since changes in perfusion will lead to alterations in nutrient and oxygen delivery which will alter tumor metabolism (balance between glycolysis and oxidative phosphorylation) and may explain differences in the resonance Raman spectra and multiphoton microscopy that occur between different tumor models. This collaborative effort is scientifically sound since the data derived at each institution is complementary and critical to addressing the issue of detecting breast tumors by optical techniques, and understanding the mechanism behind these findings. It also represents a continuation of a successful collaboration making use of the scientific resources of both institutions to enhance breast cancer care and to provide opportunities for under- represented minorities at CCNY to have access to both the scientific and clinical resources at MSKCC. Thus, MSKCC studies of perfusion and lactate metabolism are critically complementary to Drs. Shi/Alfano's studies at CCNY to understand the mechanism behind differences in tumor metabolism. This will allow this methodology to be expanded to other types of breast cancer and eventually to the clinic. Dr. Koutcher's laboratory, particularly Dr. Ackerstaff, at MSKCC has developed the methodologies to relate tumor perfusion to the microenvironment and to quantitate lactate concentrations. Drs. Alfano/Shi are uniquely suited for performing the optical studies, having implemented the necessary technology to perform their experiments.